Israel Medical Association Journal

Chronic disease management has been a rapidly growing entity in the 21st century as a strategy for managing chronic illnesses in large populations. However, experience has shown that disease management programs have not been able to demonstrate their financial value. The objectives of disease management programs are to create quality benchmarks, such as principles and guidelines, and to establish a uniform set of metrics and a standardized methodology for evaluating them. In order to illuminate the essence of disease management and its components, as well as the complexity and the problematic nature of performing economic calculations of their profitability and value, we collected data from several reports that dealt with the economic intervention of disease management programs. The disease management economic evaluation is composed of a series of steps, including the following major categories: Data/information technology, information generation, assessment/recommendations, actionable customer plans, and program assessment/reassessment. We demonstrate the elements necessary for economic analysis. Disease management is one of the most innovative tools in the managed care environment and is still in the process of being defined. Therefore, objectives should include the creation of quality benchmarks, such as principles and guidelines, and the establishment of a uniform set of metrics and a standardized methodology for evaluating them.

Background: Diseases causing increased pulmonary pressure will subsequently cause a dilation of the pulmonary arteries and right heart chambers.

Objectives: To assess the capability of computed tomography angiography and high resolution CT to diagnose and estimate the severity of pulmonary arterial hypertension as compared with standard means of right heart catheterization, echocardiography and pulmonary function tests.

Methods: The study included 38 patients with PHT[1] who underwent CT angiography and HRCT[2] as part of their routine evaluation. Diagnose included: primary PHT (n=20), Eisenmenger syndrome (n=6), scleroderma (n=3), thromboembolic disease (n=3), and others (n=6). Mean pulmonary artery pressure was 58 mmHg (range 39–92 mmHg) by catheterization and peak systolic pressure 79 mmHg (range 40–135) by echocardiography. Findings for the diameters of the main pulmonary artery and its main branches, the ascending aorta, the right atria and ventricle as well as the position of the interventricular septum were compared with 22 chest CT scans as compared to patients with no known clinical history of pulmonary hypertension, performed for other reasons (trauma, oncology follow-up) during the study period. Correlations were also calculated with recent right heart catheterization, echocardiography and pulmonary function tests of the study group.

Results: Mean main pulmonary artery diameter in the study group was 3.55 ± 0.66 cm, pulmonary artery/ascending aorta ratio 1.2 ± 0.29, right pulmonary artery 2.63 ± 0.49 cm, left pulmonary artery 2.57 ± 0.5 cm. All diameters were significantly different from the control group (P < 0.0001). Main and right pulmonary artery diameters correlated to the pressure measurement by echocardiography (P = 0.001). Bronchial collaterals were found in 11 patients (30%). The position of the interventricular septum correlated well with the echocardiography study.

Conclusions: The size of the main pulmonary artery on CT angiography has a good predictive value regarding the severity of PHT.

Background: Fanconi anemia complementation group C and Bloom syndrome, rare autosomal recessive disorders marked by chromosome instability, are especially prevalent in the Ashkenazi* Jewish community. A single predominant mutation for each has been reported in Ashkenazi Jews: c.711+4A→T (IVS4 +4 A→T) in FACC[1] and BLM^Ash in Bloom syndrome. Individuals affected by both syndromes are characterized by susceptibility for developing malignancies, and we questioned whether heterozygote carriers have a similarly increased risk.

Objectives: To estimate the cancer rate among FACC and BLM^Ash carriers and their families over three previous generations in unselected Ashkenazi Jewish individuals.

Methods: We studied 42 FACC carriers, 28 BLM^Ash carriers and 43 controls. The control subjects were Ashkenazi Jews participating in our prenatal genetic screening program who tested negative for FACC and BLM^Ash. All subjects filled out a questionnaire regarding their own and a three-generation family history of cancer. The prevalence rates of cancer among relatives of FACC, BLM^Ash and controls were computed and compared using the chi-square test.

Results: In 463 relatives of FACC carriers, 45 malignancies were reported (9.7%) including 10 breast (2.2%) and 13 colon cancers (2.8%). Among 326 relatives of BLM^Ash carriers there were 30 malignancies (9.2%) including 7 breast (2.1%) and 4 colon cancers (1.2%). Controls consisted of 503 family members with 63 reported malignancies (12.5%) including 11 breast (2.2%) and 11 colon cancers (2.2%).

Conclusions: We found no significantly increased prevalence of malignancies among carriers in at least three generations compared to the controls.

Background: The measurement of maternal serum human chorionic gonadotropin as a predictor of fetuses with Down syndrome has been in use since 1987.

Objectives: To determine the correlation between extremely high levels of hCG[1] at mid-gestation and maternal and fetal complications.

Methods: The study group consisted of 75 pregnant women with isolated high levels of hCG (> 4 MOM) at mid-gestation, and the control group comprised 75 randomly selected women with normal hCG levels (as well as normal alpha-fetoprotein and unconjugated estriol levels). The data collected included demographic details, fetal anomalies, chromosomal aberrations, pregnancy complications, and results of neonatal tests.

Results: There was a significant increase in the frequency of fetal anomalies (detected by ultrasound), low birth weight and neonatal complications in the study group. We also found an increased rate of fetal/neonatal loss proportional to the increasing levels of hCG (up to 30% in levels exceeding 7 MOM).

Conclusion: Our study demonstrated an increased frequency of obstetric complications that was closely associated with raised hCG levels. The study also raises questions about the accuracy of the Down syndrome probability equation in the presence of extremely high levels of hCG where data on the frequency of Down syndrome is severely limited.

Background: Drug-induced thyrotoxicosis is not uncommon. It may worsen life-threatening arrhythmias and may be refractory to medical treatment. Near-total thyroidectomy presents a valid alternative to medical therapy and should be considered early in the management of the disease.

Objectives: To assess whether near-total thyroidectomy was a viable approach for our patients.

Methods: Twelve patients – 7 men and 5 women, aged 63 to 82 years – presented with drug-induced fulminant thyrotoxicosis following 1 to 12 months of amiodarone treatment (11 patients, mean 7 months) and after a 6 months course of interferon-alpha treatment (one patient). Medical therapy included propylthiouracil in doses up to 1200 mg/day in all patients and a beta-receptor antagonist in seven. Five patients had to stop amiodarone treatment and start high doses of steroids. A thyroid scan was performed in all patients using 5 mCi of Tc-99m pertechnetate. The thyroid scan showed absent uptake of the tracer in the thyroid bed in all patients, precluding the use of radioablation.

Results: Four patients (three with AIT[1] and one with interferon therapy) who did not respond to 3 months of medical therapy required surgical thyroidectomy due to severe unremitting thyrotoxicosis. A near-total thyroidectomy resulted in rapid correction of thyrotoxicosis, enabling continuation of the anti-arrhythmic drug. There were no intraoperative or postoperative arrhythmias. Subsequently, all patients recovered rapidly and remained well and euthyroid on thyroxine replacement therapy.

Conclusions: Since surgery results in rapid control of thyrotoxicosis and permits continued therapy with amiodarone, we suggest that near-total thyroidectomy warrants consideration as a definitive treatment for resistant amiodarone or interferon-induced thyrotoxicosis.

Background: Decreased lacrimal gland output may cause dry eye syndrome. Using a rat model, we examined the feasibility of transplanting lacrimal gland cells from newborns.

Objectives: To restore lacrimal gland function in eyes with compromised tear production.

Methods: A model of dry eye in adult rats was developed by unilateral surgical removal of the main lacrimal gland. Tear secretion in both eyes was then assessed by masked Schirmer's test. Lacrimal gland tissue from newborn rats was transplanted into the fibrous connective tissue in which the lacrimal gland had been embedded. Masked Schirmer's test was repeated 4, 8 and 12 weeks after transplantation.

Results: Schirmer's test performed in 13 rats 10 days after unilateral lacrimal gland excision revealed significantly less wetting on the side with excised gland compared with the normal side (P < 0.003). The lack of secreting cells on the operated side was verified histologically. The reduction in tear secretion on the operated side remained significant for 8 weeks on average. In the six rats with transplanted lacrimal gland tissue however, there were no differences in tear reduction between the two eyes at 4, 8 or 12 weeks after the operation (P = 0.81, 0.56 and 0.8, respectively).

Conclusions: Transplantation of lacrimal gland tissue from newborn rats effectively restored eye wetting in this new model. Further research is needed to evaluate this new approach for treating lacrimal gland dysfunction. Using this model might also facilitate evaluation of potential clinical treatments for dry eyes.
 

Objectives: To describe patients with initially misdiagnosed PTP[1] and to emphasize the diagnostic pitfalls of this disorder.

Patients and Results: During a period of 11 years we have diagnosed six patients with PTP, four women and two men. The incidence of PTP was approximately 1:24,000 blood components transfused. We present the detailed clinical course of three of the six patients in whom the diagnosis was particularly challenging. The patients were initially misdiagnosed as having heparin-induced thrombocytopenia, systemic lupus erythematosus complicated by autoimmune thrombocytopenia, and disseminated intravascular coagulation. A history of recent blood transfusion raised the suspicion of PTP and the diagnosis was confirmed by appropriate laboratory workup.

Conclusions: PTP seems to be more frequent than previously described. The diagnosis should be considered in the evaluation of life threatening thrombocytopenia in both men and women with a recent history of blood transfusion.

In Israel, updating of the National List of Health Services is performed on a yearly basis in a systematic and structured mechanism for almost a decade. The existence of such a mechanism is vital for keeping medicine up to date, since many innovative and breakthrough medical technologies continuously and frequently evolve. The 2006 update is unique in several aspects, relating both to the mechanism and to the decision-making process. In this article we describe notable issues that arose during the current process: modifications to the update mechanism, the four-phase increase in allocated resources to fund the addition of new medical technologies (including the addition of finances at the expense of the 2007 planned budget), and public funding for high-cost therapies. Finally, we discuss the impact of medical advances on healthcare costs and a suggested constant annual addition to the budget.

Background: Endobronchial stents are used to treat symptomatic patients with benign or malignant airway obstructions.

Objectives: To evaluate the safety and outcome of airway stent insertion for the treatment of malignant tracheobronchial narrowing.

Methods: The files of all patients with malignant disease who underwent airway stent insertion in our outpatient clinic from June 1995 to August 2004 were reviewed for background data, type of disease, symptoms, treatment, complications, and outcome.

Results: Airway stents were used in 34 patients, including 2 who required 2 stents at different locations, and one who required 2 adjacent stents (total, 37 stents). Ages ranged from 36 to 85 years (median 68). Primary lung cancer was noted in 35% of the patients and metastatic disease in 65%. Presenting signs and symptoms included dyspnea (82%), cough (11.7%), hemoptysis (9%), pneumonia (5.9%), and atelectasis (3%). The lesions were located in the left mainstem bronchus (31%), trachea (26%), right mainstem bronchus (26%), subglottis (14.3%), and bronchus intermedius (2.9%). Conscious sedation alone was utilized in 73% of the patients, allowing for early discharge. Eighteen patients (50%) received brachytherapy to the area of obstruction. Complications included stent migration (one patient) and severe or minimal bleeding (one patient each). Ninety-four percent of the patients reported significant relief of their dyspnea. Three of the four patients who had been mechanically ventilated before the procedure were weaned after stent insertion. Median survival from the time of stent placement was 6 months (range 0.25–105 months).

Conclusion: Stent placement can be safely performed in an outpatient setting with conscious sedation. It significantly relieves the patient's symptoms and may prolong survival.
 

Objectives: To determine whether reliable data could be obtained at lower cost.

Methods: The study sample consisted of 50 patients with mild to severe stable COPD]1[. All underwent pulmonary function test and the cardiopulmonary exercise test, 6 minute walk and 15 step exercise oximetry test as part of their regular follow-up visit. Functional capacity was graded according to each test separately and the functional capacities obtained were correlated.

Results: The results showed that most of the patients had severe COPD according to pulmonary function tests (mean forced expiratory volume in the first second 46.3 ± 19.9% of predicted value). There was a good correlation between the cardiopulmonary exercise test and the 6 minute walk functional capacity classes (r = 0.44, P = 0.0013). We did not find such correlation between the 15 step exercise oximetry test and the cardiopulmonary exercise test (r = 0.07, P = 0.64).

Conclusions: The study shows that the 6 minute walk is a reliable and accurate test in the evaluation of functional capacity in COPD patients.

Objectives: To evaluate the national Israeli experience with lung transplantation in patients with CF[1].

Methods: We reviewed the medical charts of all CF patients who underwent lung transplantation between January 1996 and June 2005 at the two Israeli centers that performed this procedure.

Results: Eighteen transplantations were performed in 17 patients. Mean patient age at transplantation was 25.3 ± 9.1 years, and mean duration of follow-up in survivors (n=14) was 37.2 months (range 1–113 months). The actuarial survival rate was 88% at 1 year and 74% at 5 years. Pulmonary function, expressed as percent of predicted normal forced expiratory volume in 1 sec, improved from 22.4 ± 8.1% to 76 ± 16.8% at one year after transplantation. Bronchiolitis obliterans syndrome was diagnosed in 5 patients (29%), of whom 2 died and 2 are currently candidates for retransplantation. Median time to onset of BOS[2] was 34.2 months (range 17–64 months).

Conclusion: In Israel, the early and intermediate-term results of lung transplantation for cystic fibrosis are encouraging. BOS remains a major complication that threatens long-term outcome.

Background: New drugs have significantly improved the prognosis and quality of life of patients with pulmonary arterial hypertension. However, PAH[1] associated with autoimmune disease, particularly progressive sclerosis, remains a very serious problem

Objectives: To evaluate whether the course of the disease and survival is significantly different in patients with PAH related to autoimmune disease as compared to other patients with PAH and to determine the prognostic factors in these patients.

Methods: We retrospectively compared 24 patients with PAH associated with autoimmune disease to 42 patients with other causes of PAH. We focused on the clinical and hemodynamic parameters and on the outcome.

Results: The early mortality rate was slightly higher in patients with PAH associated with autoimmune disease (13% after the first year, 25% after the fifth year). The prognostic factor was a shorter distance on the 6 minutes walking distance test (r = 0.2, P = 0.01).

Conclusions: The early detection of PAH associated with autoimmune disease should encourage earlier and more aggressive treatment than in idiopathic PAH.